Continuous infusion of interleukin-1 beta in rats induces a profound fall in plasma levels of cholesterol and triglycerides.

Hermus, A.R.M.M.; Sweep, C. G. J.; Demacker, P.N.M.; Meer, M.J.M. van der; Kloppenborg, P. W. C.; Meer, J.W.M. van der

doi:10.1161/01.atv.12.9.1036

Cited by 15 publications

(10 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acute decreases in cholesterol levels occur in response to IV administration of pro-inflammatory cytokines such as IL-1β (Hermus et al 1992), IL-2 (Wilson et al 1989) and TNF-α (Ettinger et al 1992). Elevations in soluble interleukins-2 and -6 receptors (Maes et al 1995) and positive acute phase proteins (Maes et al 1997) during manic episodes have been reported, similar to what has been observed during depression (Maes 1993, Kronfol andRemick 2000).…”

Section: C) D)mentioning

confidence: 67%

Hypocholesterolemia during mixed manic episodes

Cassidy

Carroll

2002

European Archives of Psychiatry and Clinical Neurosciences

View full text Add to dashboard Cite

show abstract

Section: C) D)mentioning

confidence: 67%

Hypocholesterolemia during mixed manic episodes

Cassidy

Carroll

2002

European Archives of Psychiatry and Clinical Neurosciences

View full text Add to dashboard Cite

show abstract

“…As described in detail previously, studies of this nature are scarce despite a vast literature on the acute effects of IL-1 on lipoprotein metabolism in animal models and on responses of cultured arterial wall cells to exogenous IL-1. Previous studies of chronic administration of cytokines were conducted for only 1 wk (7,8), whereas in the current study, the time period was 1-3 mo. In addition, this study has shown that the IL1-ra protein is present in the arterial wall of murine atherosclerosis models, consistent with recent findings in human lesions (20) and supportive of the hypothesis that cytokine influences on atherosclerosis are subject to local regulation by this molecule.…”

Section: Discussionmentioning

confidence: 97%

“…Similarly, IL-1 and TNF␣ injections in rabbits and rodents can acutely increase plasma LDL (6). Interestingly, two previous studies involving continuous administration for 1 wk of either IL-1␤ or TNF␣ demonstrated decreased triglyceride levels, and at high doses of IL-1␤, decreased plasma cholesterol levels as well (7,8). There are very few studies on lipoprotein changes in chronic inflammation or chronic cytokine exposure in animal models, and observations in humans with chronic diseases such as rheumatoid arthritis and systemic lupus erythrematosis are complicated by the effects of anti-lipoprotein autoantibodies and anti-inflammatory drugs.…”

mentioning

confidence: 92%

Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size

Devlin

Kuriakose

Hirsch

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

138

View full text Add to dashboard Cite

Inflammatory cytokines have been linked to atherosclerosis by using cell culture models and acute inflammation in animals. The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra). IL-1ra knockout C57BL͞6J mice fed a cholesterol͞cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls. IL-1ra transgenic͞low-density lipoprotein receptor (LDLR) knockout mice fed a cholesterol-saturated fat diet for 10 wk showed a 40% increase in nonhigh-density lipoprotein cholesterol, consistent with the IL-1ra knockout data, although there was no change in lesion size. When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol͞high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene. By immunohistochemistry, IL-1ra was present in C57BL͞6J and LDLR knockout aortae, absent in IL-1ra knockout aortae, and present at high levels in LDLR knockout͞IL-1ra transgene aortae. In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size. These data demonstrate that in selected models of murine atherosclerosis, chronic IL-1ra depletion or overexpression has potentially important effects on lipoprotein metabolism and foam-cell lesion development.

show abstract

“…In human and nonhuman primates inflammatory stimuli as well as individual cytokines consistently cause hypocholesterolemia, 1 -8 ' 11 -' 5 whereas the acute effect in rodents of inflammation and cytokines is either an increase or no change in cholesterol levels.io.WM9.so The time course of study also appears to be an important determinant of the metabolic response to cytokines, as long-term administration of IL-1/9 to rats results in hypotriglyceridemia and hypocholesterolemia, which is the opposite of the short-term effects of cytokines in rodents. 51 LCAT activity was decreased in the medium of cells incubated with cytokines. Although we did not measure LCAT mass in our experiments, a previous report indicates 2 * that LCAT activity and mass are correlated in the medium of Hep G2 cells.…”

Section: Il-6 Concentrationmentioning

confidence: 90%

Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells.

Ettinger

Varma

Sorci‐Thomas

et al. 1994

Arterioscler Thromb

172

102

View full text Add to dashboard Cite

Cytokines, important biochemical mediators of inflammation, cause a rapid fall in the plasma concentration of cholesterol in vivo. One mechanism by which cytokines may cause acquired hypocholesterolemia is by decreasing the hepatic synthesis and secretion of apolipoproteins. To test this hypothesis, we incubated Hep G2 cells with human recombinant tumor necrosis factor-a, interleukin-1/3, and interleukin-6. Each of the cytokines resulted in a dose-related reduction in the concentrations of apolipoprotein (apo) A-I, apoB, and lecithin:cholesterol acyltransferase (LCAT) activity in the medium after 24 hours of incubation. The effect of cytokines on apolipoprotein accumulation was not affected by preincubation of Hep G2 cells with fatty acids. Cytokines decreased the concentration of cellular apoA-I mRNA in a dose-related fashion but did not affect cellular concentrations of apoB mRNA. The concentrations of triglyceride and cholesterol were also reduced in the medium of cells incubated with cytokines. Total cell sterol synthesis rates were calculated by [ 14 C]acetate incorporation. Cells incubated with interleukin-6 had a 31% increase in sterol synthesis rate but a 41% decrease in sterol secretion. These data suggest that these cytokines can decrease the hepatic synthesis and/or secretion of apolipoproteins and that this may explain, in part, the acquired hypocholesterolemia seen during acute and chronic inflammation. A cute and chronic inflammation cause hypocholes-/ \ terolemia in humans and nonhuman pri--Z \ -mates. 17 Many of the effects of inflammation on lipoprotein metabolism appear to be mediated by cytokines.8 -17 Injection of interleukin-2, colony stimulating factor, or interferon results in hypocholesterolemia in humans, 11 ' 1314 whereas tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) cause a rapid fall in plasma cholesterol as well as the concentrations of apolipoprotein (apo) A-I and apoB in nonhuman primates.The effects of cytokines on lipoprotein metabolism are complex, and the mechanisms by which cytokines cause hypocholesterolemia have not been studied extensively. However, at least two changes in lipoprotein metabolism appear to be important in the development of acquired hypocholesterolemia from inflammation in primate species. First, the metabolism of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles is altered by inflammation; concentrations of both particles fall rapidly after injection of lipopolysaccharide and cytokines. Data from Schectman et al 11 suggest that inflammation causes a decrease in LDL production rates, as injection of interferon into normocholesterolemic humans reduced the LDL-apoB production rate but did not change the fractional catabolic rate. Second, injection of lipopolysaccharide and cytokines into nonhuman primates results in a significant reduction in the cholesterol ester content of HDL and LDL that is preceded by a rapid fall in the plasma concentration of lecithin:cholesterol acyltransferase (LCAT), suggesting that acute ...

show abstract

Continuous infusion of interleukin-1 beta in rats induces a profound fall in plasma levels of cholesterol and triglycerides.

Cited by 15 publications

References 51 publications

Hypocholesterolemia during mixed manic episodes

Hypocholesterolemia during mixed manic episodes

Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size

Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells.

Contact Info

Product

Resources

About